The document summarizes the International Academy of Cytology (IAC) System for classifying breast malignancy based on fine-needle aspiration cytology (FNAC) results. The system was developed at a meeting in Yokohama in 2016. It aims to standardize breast cytology reporting to improve diagnosis and patient management. The system categorizes FNAC results as insufficient, benign, atypical, suspicious of malignancy, or malignant, with associated risks of malignancy. Cytological features and management recommendations are provided for each category. The goal is to link cytology reports to optimal breast care.

1. IAC Classification Of
Breast Malignancy- The
YOKOHAMA SYSTEM
Presented By: Dr. Ritika Hooda
BPS GMC(W) Sonepat

3. • The International Academy of Cytology (IAC) System
for Reporting Breast Fine-Needle Aspiration Cytology
(FNAC) has been developed following an initial
meeting at the Yokohama International Congress of
Cytology in 2016, by a group of cytopathologists,
radiologists, surgeons and oncologists expert in the
management of breast lesions.

4. • In the developing world, breast FNAC is still one of
the most common procedures and is increasingly
used as a key element in the screening campaign to
reduce breast cancer mortality rates.

5. Advantages of breast FNAC
• Rapid, accurate and highly cost-effective diagnostic
procedure with a minimal complication rate for the
broad spectrum of benign and malignant breast
lesions.
• High sensitivity in the range of 90–95% and a high
positive predictive value (PPV) approaching 100% for
the diagnosis of breast carcinoma.

6. Triple test
• Comprises of CLINICAL, IMAGING AND FNAC
CYTOLOGY.
• PPV(positive predictive value) close to 100%.

7. Core needle biopsy(CNB)
• CNB offers advantages in
Definitively diagnosing invasive carcinoma
Assessing mammographically detected
calcifications
Assisting with proliferative lesions.
• But it is also a sampling device similar to
FNAC.

8. Disadvantages of CNB
• CNB is more invasive, time consuming.
• Has a higher rate of complications
• Has a greater cost for both the biopsy
equipment and the required histopathological
laboratory processing and reporting
• Rare cases of needle track seeding of
carcinoma have also been reported.

9. Aims of the system
• To standardize and improve the reporting of
breast cytology
• Establish best practice guidelines
• Improve training in the performance and
interpretation of breast cytology
• Clarify communication between cytopathologists
and breast clinician
• To link this reporting system with patient
management so as to facilitate optimal breast
care

10. Present Systems for reporting breast
FNAC

11. Reporting format details
• A statement of whether the lesion is completely benign, such as
“No malignant cells are seen”.
• A statement of cellularity which is a measure of the adequacy of
the material.
• A cytological description including any diagnostic criteria or check
list of features and a brief discussion of the features which support
various possible diagnoses.
• A conclusion or summary with a standardized descriptive diagnosis
of the lesion which should point to a specific a diagnosis.
• A code or category can be placed in the body of the report but not
in the conclusion.

12. • The IAC Yokohama Reporting System
emphasizes the importance of skilled biopsy
and smear making techniques to optimize
quality and enhance FNAC diagnosis.

13. • The key elements to the breast FNAC procedure are the
 careful selection of a line of approach for the needle
 Fixation of the lesion by palpation or palpation around
an ultrasound probe
 A rapidly performed puncture of the lesion using a
rapid out from the immobilized lesion, with
appropriate use of aspiration.
 Ultrasound for guidance and visualization of the needle
tip throughout the procedure
 Good training and continued monitoring are essential

14. • The System suggests that ideally both air-dried
Giemsa-stained direct smears and alcohol-fixed
Papanicolaou stained slides should be prepared
utilizing a method of splitting the material obtained
on each needle pass. Routine rinsing of the needle or
separate passes for cell block preparation to enable
immunohistochemistry for prognostic indicators can
be utilized. Liquid-based cytology preparations can
also be considered.

15. • The IAC Yokohama System has five categories
that can be stratified by their risk of
malignancy (ROM):
Insufficient/inadequate
Benign
Atypical
Suspicious of malignancy
Malignant

16. Category- Insufficient/inadequate
• Definition: The smears are too sparsely
cellular or too poorly smeared or fixed to
allow a cytomorphological diagnosis.
• FNAC smears are regarded as adequate or
inadequate based on the assessment of the
material on the slides.
• Risk of malignancy-2.6–4.8 %

17. Adequacy criteria
• At least seven clusters each consisting of 20 or more
epithelial cells along with presence of myoepithelial
cells.
• If material is sufficient- categorize FNAC on the basis
of that material.
• However this is not the only criteria if the cytological
findings correlate with the clinical and imaging
findings in the triple test and are sufficient to make a
precise diagnosis.

18. Exceptions to the adequacy criteria
• Pus consistent with an abscess
• A proteinaceous background with or without histiocytes
consistent with cyst contents when the cyst has been drained
under imaging or has no residual mass to palpation
• fat tissue fragments consistent with a lipoma or fatty nodule,
spindle cell lesions and fat necrosis
• Reactive lymphoid material consistent with an intramammary
lymph node, or in case of a hyalinized fibroadenoma which
correlates with imaging.

19. • If no clinical or imaging information is
provided such as “completely drained cyst”
and the review of the case is not possible,
dispatch the report with the advice
“correlation with clinical and imaging findings
is required because the FNAC findings may not
represent the lesion.”

20. • If the triple assessment is discrepant and the
FNAC material does not explain the imaging or
clinical findings, then the FNAC report should
contain a statement that “the material may
not represent the lesion,” and further FNAC
or usually CNB is required.

21. Management
• Insufficient smears due to technical issues,
repeat FNAC to a maximum of three times.
• Insufficient smears due to a lack of sufficient
cellularity to explain the clinical or imaging
expected diagnosis, repeat FNAC.
• Lesion is benign on imaging- follow up after 3-6
months.
• Indeterminate or suspicious imaging- repeat
FNAC/CNB is mandatory.
• If no imaging available- correlate the clinical and
FNAC findings and repeat FNAC.

22. Category: Benign
• Definition: A benign breast FNAC diagnosis is
made in cases that have definite benign
cytological features, which may or may not
be diagnostic of a specific benign lesion.
• Risk of malignancy- 1–3%

23. Cytological features of benign lesions
• Predominantly large cohesive 3-D tissue
fragments and flat mono-layered sheets
consisting of evenly spaced, ductal epithelial
cells with myoepithelial cells creating a
“bimodal” pattern, as well as, “bare bipolar
nuclei” representing stripped myoepithelial
nuclei, in the background.

24. Common benign lesions
• Acute Mastitis
• Breast Abscess
• Granulomatous Mastitis due to TB and other
nonspecific inflammatory processes
• Foreign Body Reactions such as with silicone
• fat necrosis
• Cysts with apocrine sheets in a proteinaceous
background
• Fibrocystic Change with apocrine sheets and small
cohesive ductal epithelial tissue fragments in a
proteinaceous background

25. • Material “Consistent With Cyst Contents”
when there is a granular proteinaceous
background with no epithelium and there is
correlation with imaging and clinical findings
and the cyst completely drained
• Usual Epithelial Hyperplasia with cohesive
large ductal epithelial tissue fragments with
myoepithelial cells and with bare bipolar
nuclei in a clean background

26. • Fibroadenoma with large ductal epithelial
tissue fragments and plentiful bare bipolar
nuclei and fibrillary or rounded stromal
fragments.
• Intraductal Papilloma with large ductal
epithelial tissue fragments, along with
papillary stellate and more complex meshwork
fragments, apocrine sheets and siderophages
in a proteinaceous background

27. • Gynaecomastia resembles epithelial
hyperplasia with or without scanty stroma
• Intramammary lymph nodes show a
heterogeneous lymphoid population with
predominantly small lymphocytes.
• Lactational change with small acinar sheets of
vacuolated cells and stripped acinar nuclei in a
milky proteinaceous background including fine
fat globules

28. • Normal breast tissue showing larger ductal nuclei
with bland chromatin and smaller oval darker
myoepithelial nuclei; bare bipolar oval nuclei in
the background (Giemsa, ×400).

29. BENIGN –SUBAREOLAR ABSCESS
• A high yield of inflammatory
cells and multinucleated giant
cells.
• Keratin and squamous
metaplastic cells.
• The identification of giant
cells with keratin in
cytoplasm is an important
clue for the diagnosis.
• Reactive epithelial cells.

30. • Staghorn clusters of epithelial cells which are cuboidal
to columnar with round nuclei and fine granular
chromatin bordered by bipolar nuclei- papilloma(400x)

31. • Cyst: sheet of metaplastic apocrine cells and
histiocytes and multinucleated histiocytes in a
proteinaceous background (Giemsa,x200).

32. Fibrocystic change
• Sheets of apocrine cells slightly enlarged cohesive tissue fragments of
ductal epithelial cells with small, oval and dark myoepithelial nuclei,
oval bare bipolar nuclei and some histiocytes and multinucleated
histiocytes in a thin proteinaceous background (Giemsa, ×100).

33. • Fibroadenoma:Ductal epithelial tissue fragments, an
irregular fragment of myxoid stroma and bare bipolar
nuclei with some dispersed cells in the background; a small
aggregate of histiocytes is also present (Giemsa, ×100)

34. MANAGEMENT
• Review clinical and imaging findings:
• if “triple test” benign, no further biopsy
required, and review depends on the nature
of the lesion.
• If clinical and/or imaging indeterminate or
suspicious, repeat FNAC or proceed to CNB

35. Category: Atypical
• Definition: The term atypical in breast FNAC is
defined as the presence of cytological features
seen predominantly in benign processes or
lesions, but with the addition of some features
that are uncommon in benign lesions and
which may be seen in malignant lesions.
• Risk of malignancy- 22-39%

36. Cytological features
• High cellularity
• Increased dispersal of single intact cells
• Enlargement and pleomorphism of nuclei
• Presence of necrosis or mucin
• Complex micropapillary or cribriform
architecture of epithelial tissue fragments

37. Lesions associated
• Usual epithelial hyperplasia-by itself or
associated with fibrocystic change
• Fibroadenomas with Atypia
• Radial scars
• Intraductal papillomas
• Adenomyoepithelioma
• Spindle cell lesions

38. • Epithelial sheet showing nuclear variation in size, chromatin
and shape, multinucleation and infiltrating histiocytes,
could be regarded as atypical; but a low N:C ratio, apocrine
cytoplasmic differentiation, histiocytes and a proteinaceous
background are present (Giemsa, ×400).

39. • Dispersed cells with mildly variable nuclei could be
regarded as atypical, but they are apocrine cells with a
low N:C ratio with evidence of crush artefact in the
chromatinic smearing (Giemsa, ×100)

40. • Atypical stromal fragment showing mild hypercellularity and mild
nuclear enlargement and atypia with two ductal epithelial tissue
fragments and occasional spindle stromal cells in the background,
raising the possibility of a low-grade phyllodes tumor (Pap, ×200).

41. • Large clusters of
spindle cells
embedded in
fibromyxoid stroma.
• Individual cells are
oval to spindle
shaped with plump
fusiform nuclei

42. • Otherwise typical fibroadenoma with a (central) cohesive tissue
fragment of ductal epithelial cells with myoepithelial cells, and two
tissue fragments (right and bottom left) showing atypical crowding,
nuclear overlapping and mild nuclear enlargement. Bare bipolar
nuclei in the background (Giemsa, ×200)

43. • Epithelial hyperplasia: large cohesive irregular ductal
epithelial tissue fragment with slit-like secondary
lumina and dark oval myoepithelial nuclei in a clean
background with oval bare bipolar nuclei (Giemsa,
×100).

44. MANAGEMENT
• Atypical diagnosis due to a technical problem-
Repeat FNAC.
• If either or both the clinical and imaging findings
are indeterminate or suspicious a repeat
FNAC/CNB is mandatory.
• If neither clinical nor imaging findings are of
concern-depending on the lesion, the
management options include to repeat the
FNAC/CNB, or to review the patient with imaging
at 3–6 months, with subsequent repeat
FNAC/CNB if the lesion has changed.

45. Category: Suspicious of Malignancy
• Definition: The term “suspicious of malignancy”
in breast FNAC is defined as the presence of some
cytomorphological features, which are usually
found in malignant lesions, but with insufficient
malignant features, either in number or quality,
to make a definitive diagnosis of malignancy. The
type of malignancy suspected should be stated
whenever possible.
• Risk of malignancy- 84.6–97.1%

46. Low grade ductal carcinoma in
situ(LGDCIS)
• Highly cellular smears including a range of solid,
cribriform, micropapillary, papillary and solid papillary
subtypes
• May be associated with microcalcifications.
• Marked increase in dispersed single cells showing mild
to moderate nuclear atypia, a greatly reduced number
or total lack of myoepithelial cells associated with the
epithelial tissue fragments, and scant or absent bare
bipolar nuclei in the background.
• FNAC cannot specifically diagnose LGDCIS and at the
same time exclude invasive carcinoma

47. High-grade ductal carcinoma in situ
(HGDCIS)
• The diagnosis by FNAC is controversial as it
cannot exclude invasive carcinoma.
• HGDCIS is often associated with casting
pleomorphic calcifications on mammography, and
occasionally may produce a palpable or imaging
mass lesion in the absence of invasive carcinoma.
• May be associated with extensive necrosis,
calcifications and high-grade nuclear atypia in
dispersed single epithelial cells and both small
and larger crowded epithelial tissue fragments..

48. • The smears are often low in cellularity
reflecting the small volume of cancer cells in
ducts relative to breast tissue.
• These findings cannot exclude high grade
invasive carcinomas, particularly those of no
special type and metaplastic carcinomas,
which can also show necrosis

49. • Papillary tissue fragment consisting of thin
fibrovascular branching stroma, covered in crowded
epithelium, suggesting a papillary intraductal
carcinoma in situ; the suggested categorization is
“suspicious of malignancy” (Pap, ×100)

50. • Large epithelial tissue fragment showing a cribriform architecture,
with crowded cells, mild nuclear pleomorphism and a tendency for
the nuclei to orientate to the luminal spaces rather than stream,
suggesting cribriform intraductal carcinoma; the suggested
categorization is “suspicious of malignancy” (Giemsa, ×100).

51. • Dispersed single intact cells with large hyperchromatic pleomorphic nuclei and
occasional prominent nucleoli, juxtaposed to a ductal epithelial tissue fragment
(upper) with regular ductal nuclei and plentiful oval dark myoepithelial nuclei: the
decision to call this lesion “carcinoma” or to categorize it “suspicious of
malignancy,” because of the presence of a benign component, will depend on the
amount of malignant material (Giemsa, ×400)

52. MANAGEMENT
• A “suspicious of malignancy” FNAB cytology
diagnosis should lead to review of the imaging
findings, but further biopsy(CNB) is an
absolute requirement.
• If CNB is not available, then surgical excision
biopsy is required before specific treatment in
almost all cases.

53. Category: Malignant
• Definition: A malignant cytological diagnosis is
an unequivocal statement that the material is
malignant, and the type of malignancy
identified should be stated whenever possible.
• The malignant diagnosis should only be used
when there is a full constellation of cytological
findings and no discrepant features.
• Risk of malignancy- 99.0–100%

54. Cytological features
High cellularity
Prominent dispersal of single cells
Crowded tissue fragments with overlapping
nuclei
Nuclear enlargement
Anisonucleosis
Pleomorphism of the nuclear margin, size and
chromatin
Hyperchromasia

55. Prominent nucleoli
Tubular architecture of epithelial fragments
Intracytoplasmic lumina in atypical epithelial
cells and elastoid fragments
The presence of stromal fragments infiltrated
by carcinoma in breast smears resembling
smaller fragment seen in CNB is as being
categorical evidence of invasive carcinoma.

56. Carcinomas diagnosed most
commonly by FNAC include
• No special type(ductal)
• Lobular
• Mucinous
• Tubular
• Metaplastic carcinoma with medullary features
• Adenoid cystic carcinoma
• Carcinoma with apocrine differentiation
• Carcinoma with neuroendocrine features
• Carcinoma with osteoclastic giant cells

57. MANAGEMENT
• A malignant FNAC diagnosis should be
correlated with the clinical and imaging
findings, and if the triple test is concordant
and material is available in the cell block for
prognostic and treatment markers, definitive
therapy including neoadjuvant chemotherapy
and surgery can be commenced.

58. • If the axillary lymph nodes are palpable or
enlarged or suspicious on ultrasound of the
axilla, FNAC is recommended to stage the
patient who has presented with a breast
lesion.

59. • Dispersed single cells and discohesive small tissue
fragments of intermediate-sized cells with a high N:C ratio
and moderately enlarged and mildly pleomorphic nuclei
with small nucleoli, in a fibrillary mucinous background.
Mucinous carcinoma on histopathology (Pap, ×400).

60. • Carcinoma in fraying, discohesive tissue fragments with
high-grade, enlarged pleomorphic nuclei showing irregular
granular chromatin and nucleoli, a variable but often high
N:C ratio and a suggestion of gland formation (upper right).
Carcinoma of no specific type on histopathology (Pap,
×200).

61. • Carcinoma with intermediate-sized cells, mildly enlarged,
mildly pleomorphic nuclei (note the comparison in size to
the macrophage nucleus, top center) and eccentric
cytoplasm containing an occasional vacuole in some cells.
Lobular carcinoma on histopathology (Giemsa, ×400).

62. Ancillary Techniques
• Immunocytochemistry- diagnostic difficulties
utilizing myoepithelial cell markers on cell block
material in atypical and suspicious lesions
• Immunohistochemistry- on cell blocks for the
prognostic and predictive markers for estrogen,
progesterone and HER2 receptors.
• for the determination of a primary site in
metastatic lesions; and the study of prognostic
and predictive markers in the metastatic breast
cancer setting
• Molecular techniques- in situ hybridization for
HER2 on cell blocks

63. Thank You